Modern treatment methods have led to a major improvement in the survival rate of children with Wilms' tumor. Combined therapy using surgery, radiation therapy, and chemotherapy now cures more than 85% of patients. However, the outlook is poor for those with unfavorable histology, where the 2 year survival is less than 30%; and for those with any histology and metastases at diagnosis (about 50% survival). More effective means of treating these patients must be developed. At the same time, all treatments have their risks and complications, and refinements of therapy for those with a good prognosis are needed so as to achieve maximum survival with the least morbidity. NWTS-1 is now complete, and its primary and secondary objectives have been achieved. "Natural history" and epidemiologic information has been reported. Gross and microscopic features associated with an unfavorable outlook have been identified. Combined therapy using actinomycin-D (AMD) and vincristine (VCR) is superior to the use of either agent alone. Routine radiation therapy (RT) is not needed in all children with early stage disease. Review of RT given children with more advanced stages, however, left to be defined its role in the modern management of these patients. NWTS-2 is now in the stage of data analysis. Preliminary results suggest that 6 months of AMD and VCR maintenance therapy is satisfactory for GROUP I children, none of whom receive RT, and that the addition of adriamycin to AMD and VCR gives better results than the use of the two latter alone. NWTS-3 will build on the first two studies and use the staging system developed therefrom. The questions presently planned are: (1) Is two months of AMD and VCR maintenance therapy enough for Stage I? (2) Is RT needed for Stage II? (3) Does 1000 rad suffice for the treatment of Stage III? (4) Can a better drug regimen be devised for Stage IV and unfavorable histology? (5) What are the late adversities of successful treatment in NWTS patients?